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Patterns of Free (Unconjugated) Buprenorphine, Norbuprenorphine, and Their Glucuronides in Urine Using Liquid Chromatography-Tandem Mass Spectrometry

2012; Oxford University Press; Volume: 36; Issue: 2 Linguagem: Inglês

10.1093/jat/bkr020

1945-2403

Gwen McMillin, R. Davis, Hope Carlisle, Chantry J. Clark, Stephanie J. Marin, David E. Moody,

Poisoning and overdose treatments

Patterns of buprenorphine and metabolites were examined in 1946 positive urine samples analyzed by liquid chromatography-tandem mass spectrometry for free (unconjugated) buprenorphine and norbuprenorphine (quantitative, 2 to 1000 ng/mL) and buprenorphine-glucuronide (B3G) and norbuprenorphine-glucuronide (N3G) (semi-quantitative, 5 to 1000 ng/mL). Two distribution patterns predominated with 49.1% positive for norbuprenorphine, B3G, and N3G and 41.6% positive for buprenorphine, norbuprenorphine, B3G, and N3G. Buprenorphine, positive in 45.5% of samples, was mostly < 5 ng/mL (median 6.1 ng/mL), but 9.8% were > 1000 ng/mL. Norbuprenorphine, B3G, and N3G had semi-Gaussian distributions with medians of 64.7, 108, and 432 ng/mL, respectively. With buprenorphine < 100 ng/mL (767 samples) or ≥ 100 ng/mL (19 quantifiable samples), the respective median metabolic ratios (free norbuprenorphine/free buprenorphine) were 25.0 and 0.15. In 12 retested "> 1000 ng/mL" buprenorphine samples, free buprenorphine was 4160 to 39,400 ng/mL and free naloxone 2140 to 9560 ng/mL. In 87 subsequent samples with buprenorphine < 20 ng/mL, naloxone concentrations were < 50 ng/mL. Concentrations of buprenorphine > 100 ng/mL (particularly with low metabolite concentrations) are suspect of urine adulteration with medication (4% in the database) that can be checked in most cases by concurrent analysis for naloxone.